scholarly journals Serum lactic dehydrogenase level has prognostic value in childhood acute lymphoblastic leukemia

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 778-782 ◽  
Author(s):  
CH Pui ◽  
RK Dodge ◽  
GV Dahl ◽  
G Rivera ◽  
AT Look ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Prognostic Value ◽  
Leukocyte Count ◽  
Lymphoblastic Leukemia ◽  
Sheep Erythrocyte ◽  
Prognostic Significance ◽  
Lactic Dehydrogenase ◽  
Serum Lactic Dehydrogenase ◽  
Leukocyte Counts ◽  
Standard Risk

Abstract Serum lactic dehydrogenase (LDH) levels were measured at diagnosis in 293 children with “standard-risk” acute lymphoblastic leukemia (ALL) to determine the prognostic value of this biologic feature. Standard risk assignment was based on an initial leukocyte count of less than 100 X 10(9)/L, the absence of a mediastinal mass, the absence of meningeal involvement, and the presence of lymphoblasts lacking sheep erythrocyte receptors or surface immunoglobulin. Serum LDH levels ranged from 97 to 6,595 U/L, with a mean of 547 U/L. Higher LDH levels were associated with higher leukocyte counts, lower blast cell DNA indices, lower platelet counts, a larger spleen size, and nonwhite race. LDH levels were not related to the percentage of marrow S-phase cells, liver size, French-American-British (FAB) classification, hemoglobin levels, age, sex, or the presence of the common ALL antigen on marrow blasts. Patients with the highest LDH levels (greater than 1,000 U/L) were most likely to fail treatment, whereas those with the lowest levels (less than 300 U/L) had the lowest risk of failure (P less than .0001). The prognostic significance of serum LDH level was retained in a subset of patients that included only those with leukocyte counts less than 25 X 10(9)/L (P = .0018). When 11 presenting characteristics were subjected to multivariate analysis, serum LDH level was found to have independent prognostic strength, contributing clinically important information to that gained from leukocyte count. Early measurement of serum LDH could be useful in identifying a group of standard-risk ALL patients with a high relapse hazard.

scholarly journals Serum lactic dehydrogenase level has prognostic value in childhood acute lymphoblastic leukemia

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 778-782 ◽  
Author(s):  
CH Pui ◽  
RK Dodge ◽  
GV Dahl ◽  
G Rivera ◽  
AT Look ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Prognostic Value ◽  
Leukocyte Count ◽  
Lymphoblastic Leukemia ◽  
Sheep Erythrocyte ◽  
Prognostic Significance ◽  
Lactic Dehydrogenase ◽  
Serum Lactic Dehydrogenase ◽  
Leukocyte Counts ◽  
Standard Risk

Serum lactic dehydrogenase (LDH) levels were measured at diagnosis in 293 children with “standard-risk” acute lymphoblastic leukemia (ALL) to determine the prognostic value of this biologic feature. Standard risk assignment was based on an initial leukocyte count of less than 100 X 10(9)/L, the absence of a mediastinal mass, the absence of meningeal involvement, and the presence of lymphoblasts lacking sheep erythrocyte receptors or surface immunoglobulin. Serum LDH levels ranged from 97 to 6,595 U/L, with a mean of 547 U/L. Higher LDH levels were associated with higher leukocyte counts, lower blast cell DNA indices, lower platelet counts, a larger spleen size, and nonwhite race. LDH levels were not related to the percentage of marrow S-phase cells, liver size, French-American-British (FAB) classification, hemoglobin levels, age, sex, or the presence of the common ALL antigen on marrow blasts. Patients with the highest LDH levels (greater than 1,000 U/L) were most likely to fail treatment, whereas those with the lowest levels (less than 300 U/L) had the lowest risk of failure (P less than .0001). The prognostic significance of serum LDH level was retained in a subset of patients that included only those with leukocyte counts less than 25 X 10(9)/L (P = .0018). When 11 presenting characteristics were subjected to multivariate analysis, serum LDH level was found to have independent prognostic strength, contributing clinically important information to that gained from leukocyte count. Early measurement of serum LDH could be useful in identifying a group of standard-risk ALL patients with a high relapse hazard.

scholarly journals Response Adapted Therapy in ETV6/RUNX1-Positive Childhood Acute Lymphoblastic Leukemia Treated per Modified St Jude Total XV Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-29
Author(s):  
Mayada Abu Shanap ◽  
Iyad Sultan ◽  
Amal Abu-Ghosh ◽  
Hasan Hashem ◽  
Abdelghani Tbakhi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Induction Therapy ◽  
Leukocyte Count ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Low Risk ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Standard Risk

Introduction: ETV6-RUNX1 is the most common genetic aberration in childhood acute lymphoblastic leukemia (ALL), occurring in approximately 25% of cases with a precursor-B phenotype. The presence of ETV6-RUNX1 has been associated with a relatively low rate of relapse in multiple studies. Relapses tend to occur late and have a better salvage rate than other ALL subtypes. Moreover, conflicting data in literature regarding the prognostic significance of ETV6-RUNX1 after accounting for age, initial count and treatment intensity. We sought to study the clinical features, therapy response in newly diagnosed ETV6-RUNX1-positive treated at King Hussein Cancer Center. Methods: Patients were treated per modified St Jude Total (XV) study, risk stratification was further refined by including minimal residual disease (MRD)measurements on day 15 and day 46 of remission induction therapy. Patients with the ETV6- RUNX1 fusion or hyperdiploidy without CNS or testicular disease and a satisfactory early MRD decline (<1% on day 15 and <0.01% on day 46) were classified as being low-risk for relapse and were treated on lower -risk arm regardless of age and leukocyte count. Results: Seventy patients (n=70) with ETV6-RUNX1-positive treated at our institution between May 2006 to October 2017. The median age at diagnosis, 5.8 years (range, 1.5-10.8). ETV6-RUNX1 was associated with favorable age between 1- and 6-years in 55 patients (79%), male gender in 41 patients (59%), initial leukocyte count <10 in 39 patients (56%), CNS status 1 in 100% of patients. The majority, n= 58 (83%) of patients had NCI standard risk (SR) and n=12 (17%) had NCI high risk (HR). Sixty-six patients (94%) had MRD <1% at day 15 and all patients achieved remission with MRD<0.01% at day 46 of remission induction. All patients were treated as LR ALL per modified St Jude total XV protocol. At median follow up of (36 months; range, 26 to 154), in the subgroups of ETV6-RUNX1-positive patients classified as NCI standard risk (SR)and NCI high risk (HR) the 5-year EFS estimates were 94.1% ± 3.2 and 82%±1(P=.13), 5-year OS estimates were 100% and 92% ± 8 (p=0.31) respectively. Conclusion: MRD treatment schema in ETV6/RUNX1 -positive patients have excellent outcomes if they achieved favorable response at day 15 and end of remission induction regardless of the age and Initial leukocyte count. Treatment reduction is feasible and declared safe for children with NCI-HR who are predicted to have a low risk of relapse on the basis of rapid clearance of MRD post remission induction therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Hypodiploidy is associated with a poor prognosis in childhood acute lymphoblastic leukemia

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 247-253 ◽  
Author(s):  
CH Pui ◽  
DL Williams ◽  
SC Raimondi ◽  
GK Rivera ◽  
AT Look ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Lactic Dehydrogenase ◽  
Chromosomal Translocations ◽  
Leukemic Cells ◽  
Childhood All ◽  
Patients Âgés ◽  
Serum Lactic Dehydrogenase ◽  
Leukocyte Counts

Abstract Leukemic cells from 31 (7.6%) of 409 children with newly diagnosed acute lymphoblastic leukemia (ALL) had a hypodiploid karyotype. The patients' ages ranged from 0.8 to 17 years (median, 5 years) and their initial leukocyte counts from 1.0 to 132 X 10(9)/L (median, 12.7 X 10(9)/L). Modal chromosome numbers for the leukemic stem lines were 45 in 26 cases, 28 in two cases, and 26, 36 and 43 in one case each. Seven cases had one to three additional abnormal lines due to clonal evolution. Chromosome 20 was lost most frequently (nine cases). Structural abnormalities--including chromosomal translocations (21 cases), deletions (ten cases), duplications (two cases), or inversions (one case)--were common findings; the nonrandom translocations consisted of the t(1;19)(q23;p13.3) in two pre-B cases and tdic(9;12)(p1?1;p1?2) in three cases of common ALL. When compared with hyperdiploid cases (greater than 50 chromosomes), ALL with hypodiploidy was found to have a poorer outcome and was more likely to be associated with chromosomal translocations, higher serum lactic dehydrogenase levels, and age less than 2 or greater than or equal to 10 years. Moreover, patients with hypodiploid ALL fared as poorly as those with pseudodiploid karyotypes, even though their leukocyte counts and serum lactic dehydrogenase levels were lower and they had a comparable frequency of leukemic cell translocations. Hypodiploidy is therefore an unfavorable karyotypic feature in childhood ALL.

scholarly journals Hypodiploidy is associated with a poor prognosis in childhood acute lymphoblastic leukemia

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 247-253
Author(s):  
CH Pui ◽  
DL Williams ◽  
SC Raimondi ◽  
GK Rivera ◽  
AT Look ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Lactic Dehydrogenase ◽  
Chromosomal Translocations ◽  
Leukemic Cells ◽  
Childhood All ◽  
Patients Âgés ◽  
Serum Lactic Dehydrogenase ◽  
Leukocyte Counts

Leukemic cells from 31 (7.6%) of 409 children with newly diagnosed acute lymphoblastic leukemia (ALL) had a hypodiploid karyotype. The patients' ages ranged from 0.8 to 17 years (median, 5 years) and their initial leukocyte counts from 1.0 to 132 X 10(9)/L (median, 12.7 X 10(9)/L). Modal chromosome numbers for the leukemic stem lines were 45 in 26 cases, 28 in two cases, and 26, 36 and 43 in one case each. Seven cases had one to three additional abnormal lines due to clonal evolution. Chromosome 20 was lost most frequently (nine cases). Structural abnormalities--including chromosomal translocations (21 cases), deletions (ten cases), duplications (two cases), or inversions (one case)--were common findings; the nonrandom translocations consisted of the t(1;19)(q23;p13.3) in two pre-B cases and tdic(9;12)(p1?1;p1?2) in three cases of common ALL. When compared with hyperdiploid cases (greater than 50 chromosomes), ALL with hypodiploidy was found to have a poorer outcome and was more likely to be associated with chromosomal translocations, higher serum lactic dehydrogenase levels, and age less than 2 or greater than or equal to 10 years. Moreover, patients with hypodiploid ALL fared as poorly as those with pseudodiploid karyotypes, even though their leukocyte counts and serum lactic dehydrogenase levels were lower and they had a comparable frequency of leukemic cell translocations. Hypodiploidy is therefore an unfavorable karyotypic feature in childhood ALL.

Overexpression of LEF1 predicts unfavorable outcome in adult patients with B-precursor acute lymphoblastic leukemia

Blood ◽  
2011 ◽  
Vol 118 (24) ◽  
pp. 6362-6367 ◽  
Author(s):  
Andrea Kühnl ◽  
Nicola Gökbuget ◽  
Martin Kaiser ◽  
Cornelia Schlee ◽  
Andrea Stroux ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Pathogenetic Role ◽  
Recurrent Mutations ◽  
Risk Patients ◽  
Molecular Therapies ◽  
Standard Risk

Abstract Aberrant activation of the Wnt pathway plays a pathogenetic role in various tumors and has been associated with adverse outcome in acute lymphoblastic leukemia (ALL). LEF1, a key mediator of Wnt signaling, has been linked to leukemic transformation, and recurrent mutations of LEF1 have been identified in pediatric T-ALL. Here we evaluated the prognostic significance of LEF1 expression in B-precursor ALL patients. LEF1 expression was determined by quantitative real-time RT-PCR in 282 adult B-precursor ALL patients treated on 06/99 and 07/03 GMALL trials. Patients were grouped into quartiles (Q1-Q4) according to LEF1 expression levels (LEF1 high, Q4; n = 71; LEF1 low, Q1-Q3; n = 211). Patients with high LEF1 expression had a significantly shorter relapse-free survival (RFS) compared with low LEF1 expressers (5-year RFS: LEF1 high, 27%; LEF1 low, 47%; P = .05). Importantly, high LEF1 expression was also associated with inferior RFS in standard-risk patients and was independently predictive for RFS (P = .02) in multivariate analyses for this subgroup. Thus, high LEF1 expression identifies B-precursor ALL patients with inferior RFS, supporting a pathogenetic role of Wnt signaling in ALL. Standard-risk patients with high LEF1 expression might benefit from early treatment modifications and new molecular therapies, including agents targeting the Wnt pathway.

Concordance and Prognostic Significance of Minimal Residual Disease Detection in Peripheral Blood and Bone Marrow Samples of Infants with MLL-rearranged Acute Lymphoblastic Leukemia Treated By MLL-Baby Protocol

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2404-2404
Author(s):  
Grigory Tsaur ◽  
Alexander Popov ◽  
Tatyana Riger ◽  
Alexander Solodovnikov ◽  
Tatyana Nasedkina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Prognostic Value ◽  
Residual Disease ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Remission Induction ◽  
Gene Transcripts ◽  
Minimal Residual

Abstract Background. Minimal residual disease (MRD) is powerful tool for prediction of treatment outcome in leukemia patients of various age groups, including infants with acute lymphoblastic leukemia (ALL). In the vast majority of cases only bone marrow (BM) samples are used for MRD detection. Objective. To estimate prognostic significance of MRD in peripheral blood (PB) and BM by qualitative detection of different MLL fusion gene transcripts in infant ALL enrolled into MLL-Baby protocol. Methods. Fifty three infants (20 boys and 33 girls) with median age of 5.3 months (range 0.03-11.80) and defined MLL rearrangements were included in the current study. Among them there were 25 patients (47.2%) carrying MLL-AFF1 fusion gene transcripts, 10 (18.9%) MLL-MLLT3-positive cases, 9 (17.0%) MLL-MLLT1-positive cases, 5 (9.4%) MLL-MLLT10-positive cases and 4 (7.5%) MLL-EPS15-positive ones. MRD evaluation was performed by detection of MLL fusion gene transcripts in BM and PB samples using real-time PCR and nested RT-PCR with sensitivity non-less than 1E-04. MRD-negativity was defined as absence of fusion gene transcripts in both assays. Median of follow-up period in the observed group was 5.2 years. Time points (TP) for MRD assessment were as follows: day 15 of remission induction (TP1), at the end of remission induction (TP2), after each course of ATRA administration (TP3-TP7). Informed consent was obtained in all cases. Results. We estimated 142 paired BM/PB samples. 77 samples were double positive, 43 were double negative Thus concordance between MRD results in BM and PB samples achieved 84.5%. Concordance varied between different TPs of MLL-Baby protocol from 79.0% to 100%. The highest concordance rate was at TP4 and TP7 (92.3% and 100%, respectively). Interestingly, all discrepant results (22 samples 15.5%) were BM-positive/PB-negative. Median level of ABL gene, used for normalization, was similar in BM and PB samples (4.85E+04 vs 4.95E+04, respectively, p=0.760). Evaluation of prognostic significance of MRD in BM in TP1-TP7 revealed that TP4 was the earliest TP when discriminative data between MRD-positive and MRD-negative patients were obtained. MRD-positivity at TP4 in BM led to unfavorable outcome. Event-free survival was significantly lower in MRD-positive group (n=22) in comparison to MRD-negative one (n=31) (0.06±0.06 vs 0.70±0.09 p=0.0001), while cumulative incidence of relapse in MRD-positive patients was remarkably higher (0.92±0.01 vs 0.29±0.08, p<0.0001). MRD-positivity at this TP in BM was the only significant factor in the diagnostic model where initial risk factors (age at diagnosis, initial WBC count, immunophenotype, CNS disease, presence of MLL-AF4) were combined to response criteria (number of blast cells at day 8 of dexamethasone prophase and MRD in BM at TP4) (Table). The only TP when MRD data obtained from PB samples had prognostic value was TP6. In this TP cumulative incidence of relapse in MRD-positive patients was significantly higher in comparison to MRD-negative ones (0.88±0.11 vs 0.25±0.13, respectively, p=0.003). However these data did not bring any extra advantages as compared to TP4 in BM. Conclusions. Despite high qualitative concordance rate between MRD detection in BM and PB samples we could not show prognostic value of MRD monitoring in PB by fusion gene transcripts. Univariate and multivariate analysis revealed that MRD-positivity at TP4 in BM was the only significant and independent prognostic factor of unfavorable outcome in the observed group of patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prospective Analysis of TEL Gene Rearrangements in Childhood Acute Lymphoblastic Leukemia: A Children's Oncology Group Study

2008 ◽  
Vol 26 (13) ◽  
pp. 2186-2191 ◽  
Author(s):  
Jeffrey E. Rubnitz ◽  
David Wichlan ◽  
Meenakshi Devidas ◽  
Jonathan Shuster ◽  
Stephen B. Linda ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Oncology Group ◽  
Free Survival ◽  
Pediatric Oncology Group ◽  
Gene Status ◽  
Group Sex ◽  
Cure Rates ◽  
Standard Risk

Purpose To prospectively determine the prognostic significance of the TEL-AML1 fusion in children with acute lymphoblastic leukemia (ALL). Patients and Methods TEL gene status was determined for 926 patients with B-precursor ALL enrolled on the Pediatric Oncology Group ALinC 16 trials and patients were observed for a median time of 8 years. Results Rearrangements of the TEL gene were detected in 244 patients (26%). The estimated 5-year event-free survival rate (± SE) for patients with TEL rearrangements was 86% ± 2%, compared with 72% ± 2% for those with germline TEL (P < .0001). TEL rearrangements were associated with a superior outcome among patients with standard-risk ALL, high-risk ALL, and rapid early responses to therapy. In a multivariate analysis that included risk group, sex, and day 15 marrow status, TEL status was an independent predictor of outcome (P = .0002). Conclusion We conclude that TEL gene status should be incorporated into risk classification schemes and suggest that patients who have standard-risk features, the TEL-AML1 fusion, and rapid early responses to therapy, should be treated with antimetabolite-based therapy designed to maintain their high cure rates and avoid late effects.

scholarly journals Complications and outcome in childhood acute lymphoblastic leukemia with hyperleukocytosis

Blood ◽  
1992 ◽  
Vol 79 (4) ◽  
pp. 871-875
Author(s):  
JM Eguiguren ◽  
MJ Schell ◽  
WM Crist ◽  
K Kunkel ◽  
GK Rivera
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Remission Rate ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Lactic Dehydrogenase ◽  
Cranial Irradiation ◽  
High Dose ◽  
Continuation Therapy ◽  
Drug Induction ◽  
Leukocyte Counts

Abstract Hyperleukocytosis (greater than or equal to 100 x 10(9) leukocytes/L) was identified at diagnosis of acute lymphoblastic leukemia in 64 of 358 patients enrolled on St Jude Total Therapy Study XI from February 1984 to September 1988. These children received a seven-drug induction regimen followed by high-dose methotrexate, cranial irradiation at 1 year of remission, and 120 weeks of continuation therapy with rotational administration of four drug pairs. The 27 patients with leukocyte counts greater than or equal to 200 x 10(9)/L underwent initial cytoreduction via leukapheresis or exchange transfusions. The complete remission rate for patients with hyperleukocytosis (94%) was similar to that for the overall series (96%). Stepwise regression analysis showed that hyperleukocytosis was significantly associated with age less than 1 year at diagnosis, T-cell immunophenotype, leukemic cell ploidy less than or equal to 50 chromosomes, organomegaly, and elevated lactic dehydrogenase. The 27 patients with extreme hyperleukocytosis (greater than 200 x 10(9)/L) different from the other 37 children only in a higher frequency of French-American- British (FAB) L2 morphology. Estimated 4-year event-free survival (EFS) was 52% +/- 8% (SE) for patients with hyperleukocytosis versus 79% +/- 4% for patients with leukemic counts less than 100 x 10(9)/L (P less than .0001). Patients with leukocyte counts of 100 to 200 x 10(9)/L had a significantly better EFS than those with counts greater than 200 x 10(9)/L (64% +/- 10% v 34% +/- 14%; P = .04). Thus, the therapy in this trial proved satisfactory for children with leukocyte counts of 100 to 200 x 10(9)/L; further study is needed to improve the outlook for children with counts greater than 200 x 10(9)/L.

Lack of Prognostic Significance of Absolute Lymphocyte Count After Intensive Induction Therapy in Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4909-4909
Author(s):  
Khaldoun J. Alkayed ◽  
Faris Madant ◽  
Abdulla Ibrahim ◽  
Hadeel Halasheh ◽  
Eman Khattab ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Induction Chemotherapy ◽  
Lymphocyte Count ◽  
Prognostic Value ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Absolute Lymphocyte Count ◽  
Prognostic Effect ◽  
Post Induction

Abstract Abstract 4909 Introduction: Previous work has shown that the function and number of lymphocytes are vital for the patient's immune system to mount an effective response against cancer cells. Multiple recent studies have demonstrated the prognostic value of absolute lymphocyte count (ALC) in a wide range of malignancies. In children with acute lymphoblastic leukemia (ALL), ALC during induction chemotherapy have been shown to be an independent predictor of adverse outcome, even in the era of minimal residual disease (MRD). Most of the previous studies used Children Oncology Group (COG) based regimens with 3 or 4 drugs induction. We hypothesized that with more intensive induction regimens with 5 or 7 drugs, ALC would lose its prognostic value due to more intensive chemotherapy induced leukopenia. Patients/methods: We reviewed 136 Jordanian pediatric patients (Arabic ethnicity) with newly diagnosed ALL, age 1–18 years, from 2007 to 2009. The patients were treated at a single institution on modified St. Jude total XIII and VX protocols, with a median follow up of 35 months (range: 2–54 months). The induction phase was composed of 7 drugs regimen. Variables analyzed included ALC at diagnosis, day15, day 36 end of induction chemotherapy and at time of post induction marrow recovery, white blood cells at diagnosis, age at diagnosis, gender, immunophenotype, cytogenetics, risk group and MRD status at end of induction. ALC at each time-point was evaluated for prognostic ability by univariate and multivariate analysis. Results: We found that ALC at day15, day 36 end of induction chemotherapy and at time of post induction marrow recovery failed to have any prognostic effect on event-free survival (EFS) or overall survival (OS). We analyzed ALC as continuous and dichomatous variable, but without any prognostic significance. In contrast to our hypothesis, children with ALL intensive induction regimen did not have profound lymphopenia, with ALC day15 median of 1260 cells/ml (range: 0–9450), ALC day36 median of 866 (range: 100–3476), and ALC (post induction marrow recovery) median of 1145 cells/ml (range: 85–9676). Our cohort confirmed several known prognostic factors in childhhod ALL. For EFS outcome we found MRD35, age, phenotype and risk group to have a significant prognostic effect with P values of (0.016, 0.005, 0.006, 0.001) respectively. For OS outcome we found both age and phenotype to have a significant prognostic P value of (0.006 and <0.001) respectively. Conclusions: In this study we failed to replicate the previous work that showed the independent prognostic value of ALC during induction therapy in childhood ALL. In contrast to our hypothesis, the reason for the lack of significance was not due to more profound lymphopenia. The lack of ALC prognostic significance in our cohort could be protocol related or patient population (ethnicity) related. Further studies are needed in children with ALL with different ethnic backgrounds to validate the previous work regarding ALC significance before its incorporation in ALL prognostic models, especially in middle or low income countries. Disclosures: No relevant conflicts of interest to declare.

Outcome After Relapse Among Children With Standard-Risk Acute Lymphoblastic Leukemia: Children's Oncology Group Study CCG-1952

2007 ◽  
Vol 25 (36) ◽  
pp. 5800-5807 ◽  
Author(s):  
Suman Malempati ◽  
Paul S. Gaynon ◽  
Harland Sather ◽  
Mei K. La ◽  
Linda C. Stork
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cox Regression ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Late Relapse ◽  
Central Nervous System Relapse ◽  
Cell Transplant ◽  
Cox Regression Analysis ◽  
First Remission ◽  
Standard Risk

Purpose The event-free survival (EFS) of children with standard-risk acute lymphoblastic leukemia (SR-ALL) is now more than 80%. However, prognosis after relapse continues to be poor. We examined postrelapse outcomes of children initially treated on the Children's Cancer Group CCG-1952 study. Patients and Methods We evaluated outcomes after bone marrow (BM) relapse and isolated extramedullary (EM) relapse for 347 patients with SR-ALL (WBC < 50,000/μL; age, 1 to 9 years). The prognostic significance of several factors for EFS after relapse (EFS2) was assessed by Cox regression analysis. Stem-cell transplant (SCT) was compared with chemotherapy as salvage treatment. Results The mean ± SE times to isolated central nervous system relapse, BM relapse, and isolated testicular relapse were 23 ± 1 months (range, 1 to 88 months), 36 ± 1 months (range, 2 to 79 months), and 40 ± 2 months (range, 16 to 64 months), respectively. The estimated percent ± SE 3-year EFS2 and overall survival rates after BM relapse were 37% ± 4% and 46% ± 4%, respectively, and rates after isolated EM relapse were 57% ± 5% and 71% ± 5%, respectively. By multivariate analysis, we found the duration of first remission to be the most significant predictor of EFS2 for either BM relapse or isolated EM relapse. Outcome was equivalent with SCT or chemotherapy after early or late relapse of SR-ALL at any site. Conclusion Duration of first remission remains the most significant predictor of outcome after either BM or isolated EM relapse of SR-ALL. Prognosis after early BM relapse remains poor and is not improved with SCT in this cohort.

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